oral cancer

The US Food and Drug Administration (FDA) just added another agent, PNC-27, to the growing list of drugs that falsely claim to treat or cure cancer.

An FDA lab recently found the bacteria Variovorax paradoxus in PNC-27, a product that is claiming to treat and cure all cancers, claiming to affect lung cancer as affectively as head and neck cancer. Though no illness or serious adverse events were reported to the FDA, contact with contaminated samples can lead to life-threatening infections, especially in vulnerable populations, such as young children, elderly people, pregnant women and people who have weakened immune systems, according to a statement released by the FDA.

“In general, consumers should be cautious of products marketed and sold online claiming to treat, cure or prevent any disease. Products claiming to treat, cure or prevent disease, but are not proven safe and effective for those purposes not only defraud consumers of money, they can lead to delays in getting proper diagnosis and treatment of a potentially serious condition,” Kristofer Baumgartner, FDA spokesperson, said in an interview with CURE.

PNC-27 is being dosed in multiple ways, such as a nebulized solution, intravenous solution, vaginal suppository or rectal suppository.

The FDA is urging people not to purchase or use PNC-27, which is neither FDA evaluated or approved. Patients should consult with their licensed health care providers before deciding on a treatment plan, and if they have already taken PNC-27, they should see their doctor as soon as possible, and report any adverse events to the FDA’s MedWatch Adverse Event Reporting Program.

As a matter of policy, the FDA cannot discuss any ongoing trials in detail, Baumgartner said. – See more at: http://www.curetoday.com/articles/fda-warns-against-socalled-cancer-cure#sthash.YgMC7JgV.dpuf

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

The 69 National Cancer Institute (NCI)-designated cancer centers have issued a joint statement in support of recently revised recommendations from the Centers for Disease Control and Prevention (CDC) to improve national vaccination rates for human papillomavirus (HPV).

According to the CDC, incidence rates of HPV-associated cancers have continued to rise, with approximately 39,000 new HPV-associated cancers now diagnosed each year in the United States. Although HPV vaccines can prevent the majority of cervical, anal, oropharyngeal, and other genital cancers, vaccination rates remain low across the United States, with just 41.9% of girls and 28.1% of boys completing the recommended vaccine series.

New Recommendations

The new guidelines from the CDC recommend that children under age 15 should receive 2 doses of the 9-valent HPV vaccine at least 6 months apart. Adolescents and young adults older than 14 should continue to complete the 3-dose series.

Research shows there are a number of barriers to overcome to improve vaccination rates, including a lack of strong recommendations from physicians and parents not understanding that this vaccine protects against several types of cancer. In an effort to overcome these barriers, NCI-designated cancer centers have organized a continuing series of national summits to share new research, discuss best practices, and identify collective action toward improving vaccination rates.

The original joint statement, published in January 2016, was the major recommendation from a summit hosted at The University of Texas MD Anderson Cancer in November 2015, which brought together experts from the NCI, CDC, American Cancer Society, and more than half of the NCI-designated cancer centers.

The updated statement is the result of discussions from the most recent summit, hosted this past summer by The Ohio State University Comprehensive Cancer Center. Nearly 150 experts from across the country gathered in Columbus to present research updates and plan future collaborative actions across NCI-designated cancer centers.

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

In August 2016, the FDA approved pembrolizumab (Keytruda) for patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).1 Not only was it the first immunotherapy approved for head and neck cancer (HNC), but it marked the first new drug approval for HNC in the United States in 20 years.

“Now we have an agent that really changes the paradigm—a new class of treatment—and we are seeing amazing benefit in some patients,” said Tanguy Seiwert, MD, during an OncLive Peer Exchange® panel held during the 2016 European Society for Medical Oncology (ESMO) Annual Meeting.

Less than a month later, the menu of immunotherapy options expanded as the FDA approved nivolumab (Opdivo) for the treatment of patients with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy.

During the Peer Exchange, the panelists provided an overview of the immunotherapy terrain in HNC, a discussion that was filled with considerable hope and excitement. “When we try immunotherapies in the second-line setting, we see objective responses—sometimes deep, clinically meaningful, extremely durable responses—and we’re beginning to think that maybe, on some occasions, we may be able to cure patients with relapsed metastatic head and neck cancer,” said Kevin Harrington, MD, PhD. This is especially remarkable since such patients have generally had a survival of ≤1 year.

The panelists concurred that the care of patients with HNC will evolve significantly over the next 5 to 10 years, as the tip of the immunotherapy iceberg is just starting to be scratched. During the Peer Exchange, they provided a rationale for using immunotherapies in HNC, including human papillomavirus (HPV)-positive and HPV-negative disease; outlined key immunotherapy studies; and offered their thoughts on the future of immunotherapies in HNC, including use of biomarkers to guide therapy and the opportunity to improve response by using combination treatments.

“Next-generation sequencing efforts are beginning to shed light on the hidden complexities of these tumors, leading to the identification of multiple molecular subtypes,” said Ezra Cohen, MD, who served as moderator for the session. “As key differences between tumors, with and without HPV infection, are beginning to emerge, the challenge is to find ways to use this information to personalize treatment for individual patients.”

Rationale for Immunotherapy in HNC

In patients with locally advanced HNC, HPV status has generally determined outcomes, with HPV-positive patients having a good prognosis and higher likelihood of cure, and HPV-negative patients having a poorer prognosis and a lower likelihood of cure.

However, outcomes with conventional therapy in recurrent metastatic disease have been poor across the board, especially in the setting of platinum- refractory disease, indicating a tremendous unmet need. Before pembrolizumab was approved in this setting, the recommendation was to use a taxane, such as methotrexate or cetuximab (Erbitux), as a single agent, but the outcomes have been unsatisfactory. In contrast, immunotherapy studies have shown promising results in these patients, with HPV-negative patients also benefiting.

“The rationale for [using immunotherapies] for HPV-positive tumors may be the virus, as well as mutations, and for HPV-negative tumors, it’s likely the mutation load,” said Seiwert. He explained that HPV-negative tumors are often smoking-associated tumors and, therefore, have high mutation loads, a factor that has been associated with good response to immunotherapy, whereas HPV-positive tumors resemble melanoma, with significant inflammation, another factor associated with good response.

Although efficacy was found to be the same for HPV-positive and HPV-negative tumors in KEYNOTE-012, which was the study that led to pembrolizumab’s approval for HNC, some CheckMate-141 subanalyses suggest there might be slightly more activity in HPV-positive patients, noted Seiwert.

Despite such findings, he said, “HPV status should not actually dissuade us one way or the other from using immunotherapy—it’s clearly active in both HPV-negative and HPV-positive tumors.” And, as Harrington pointed out earlier in the discussion, since nothing else works well in the second-line setting, “why not try it?”

Key Pembrolizumab Studies

The panelists proceeded to provide an overview of several instrumental pembrolizumab studies, including the KEYNOTE-012 expansion study and KEYNOTE-055 studies, and of the phase III CheckMate-141 study, which paved the way for nivolumab’s approval.2-4 They also discussed a subanalysis of CheckMate-141 presented at ESMO that demonstrated good patient-reported outcomes following nivolumab therapy, lending further support to its use in SCCHN.5

Pembrolizumab was well tolerated, and yielded a clinically meaningful ORR with evidence of durable responses; median duration of response was not reached. The ORR was 18% by central imaging vendor review and 20% by investigator analysis. A statistically significant increase in ORR was observed for PD-L1–positive versus PD- L1–negative patients (22% vs 4%, respectively; P = .021).

At 6 months, PFS and OS rates were 23% and 59%, respectively. “And we have patients living far beyond what we usually expect for metastatic disease…we now have patients who have completed 2 years of treatment in a setting with a median life expectancy of about 6 months,” revealed Seiwert, who is involved with the study.

Pembrolizumab was also well tolerated. Grade ≥3 events occurred in 9% of patients. “[This is] within the range of toxicities that we have seen in other studies,” said Viktor Grünwald, MD. “Because we’re approaching a very sick and morbid patient population, we might expect different toxicity outcomes, so I think it’s very reassuring that we’re seeing the same amount of toxicity as in other studies,” he explained.

While checkpoint inhibitors are generally well tolerated and have favorable toxicity profiles, the panelists warned that severe side effects can occur and careful patient monitoring is required. A key concern they discussed is pneumonitis.

“Although it only occurs in about 1% to 2% of patients, you must screen for it because it’s life threatening,” said Seiwert. “If somebody says, ‘I am short of breath’ or ‘I have a little bit of a cough,’ I scan them right away to look for it,” he said, explaining that immediate treatment with high-dose steroids is warranted.

KEYNOTE-055 Preliminary Results

KEYNOTE-055 enrolled 172 patients with recurrent or metastatic SCCHN to receive pembrolizumab 200 mg every 3 weeks after progression on platinum plus cetuximab. The preliminary analysis, which reported on 92 evaluable patients, was initially presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.3 Primary endpoints include ORR and safety.

As with KEYNOTE-012, pembrolizumab was found to be well tolerated and to have significant antitumor activity, with 17% to 18% response rates. Evaluation of the full study cohort will include analyses of HPV status and response by anatomic site. “I think that’s the story we’re seeing for pembrolizumab in head and neck cancer—patients are already being treated in single-arm clinical studies, which is somewhat unusual, but reflects the speed of knowledge that we’re gaining that is leading to approvals,” said Grünwald.

Nivolumab also had a lower incidence of treatment-related adverse events (TRAEs) than IC. Any grade TRAEs occurred in 59.3% and 77.5% of patients on nivolumab or IC, respectively. Grade 3/4 TRAEs occurred in 13.6% and 35.1% of patients, respectively, indicating the treatment is well tolerated, which also translated to improvements in quality of life in the patient-reported outcomes study.5

“A very detailed analysis of patient-reported outcomes using 3 well-validated questionnaires showed nivolumab was able to maintain good patient-re- ported outcomes in terms of their quality of life, their functioning, and their symptom scores, whereas IC showed serious detriment in those scores,” said Harrington.

In the study,5 patients treated with nivolumab had delayed worsening of functioning and symptoms compared with IC at approximately 4 months of follow-up, with patients receiving nivolumab reporting longer maintenance of function and less pain, fatigue, and dyspnea on treatment, as compared with those receiving IC.

“So not only do we have clear evidence that these drugs can work in terms of improving survival and delivering meaningful responses, but they do so with fewer episodes of treatment-related toxicity and disease-associated morbidity,” said Harrington.

Future of Immunotherapy in HNC

The panelists noted that use of biomarkers and combination therapies are key areas of future development for HNC. Both areas are already being examined in clinical trials and have relevance across the vast HNC spectrum, from those with minimal disease to those with previously treated advanced disease, potentially offering a curative pathway to more patients.

“It’s fantastic to have drugs that work in second-line relapsed metastatic or first-line metastatic setting, but what I want and what patients want is to be cured at the time they first present with their disease so they never have treatment in relapsed metastatic setting,” said Harrington.

Biomarkers

Although biomarkers such as PD-L1 expression are already being used and can help identify patients who are more likely to respond, high PD-L1 expression does not guarantee response, nor does no or low PD-L1 expression ensure lack of response or lack of durable response.

Subsequently, use of pembrolizumab and nivolumab is without use of this biomarker for patient selection. “While [a PD-L1 assay] can help inform patients of their likelihood to respond, it is not an assay that can select patients,” said Seiwert, who is working to identify novel biomarkers.

“I’ve been involved in looking at a novel biomarker called interferon gamma signature, which can be assayed quite easily with a rapid turn-around, and seems to perform somewhat better than PD-L1 expression,” said Seiwert. “It seems to have a high negative predictive value, and it may eventually allow us to exclude some patients who have no chance of having benefit, but it needs further validation.” He said that other biomarkers are also under investigation, including mutational load, immunogenic mutations, and dynamic biomarkers, but all are still experimental.

“What we really need is a biomarker that would predict progressive disease,” said Grünwald. “To me, that would be much more usable than an assay that just allows us to say to patients ‘your chance of response is 30%.’ I see biomarkers as having the potential to guide development of treatment algorithms,” he said.

Combinations

Currently, PD-L1–targeted agents have seen the greatest development, and studies are starting to suggest that response with these agents can be enhanced when they are combined with other treatments, including chemotherapy, CTLA-4 blockade, and radiotherapy. “About 70% of HNCs have some level of PD-L1 expression—some level of inflammation—but we only see responses in 15% to 18% of patients, so the pool of patients who might benefit from combinations is huge,” said Seiwert.

He noted that the melanoma and lung cancer settings have already shown combining PD-1 inhibitors with chemotherapy or a second checkpoint inhibitor to be particularly promising in the front line, and he suspects one or both combinations will eventually receive approval in these settings and warrant serious investigation for patients with SCCHN.

“Some of our patients do not benefit from a checkpoint inhibitor, and we can’t identify these patients in advance, but giving them chemotherapy might buy us time,” he said. “It’s almost like a pharmacodynamic effect, where we have more time for the immunotherapy to work, and maybe, also make the immune system stronger and expose antigens.”

In the locally advanced setting, animal studies have shown promise combining chemoradiotherapy with immunotherapy, but results of a small study presented at ESMO revealed some dosing challenges in humans.6

In the study, 18 patients with various forms of intermediate- or high-risk SCCHN received ipilimumab, an anti–CTLA-4 antibody, in addition to standard intensity-modulated radiotherapy with cetuximab. Dermatologic immune-related adverse events limited dosing. “There are some safety hints that it may not be a piece of cake getting through radiotherapy, and maybe cetuximab might not be the optimal part now, but I think there is still a lot of promise combining radiochemotherapy with immunotherapy,” said Grünwald. “It could be a future way in how we successfully treat early forms of localized SCCHN.”

Combining checkpoint inhibition with radiation is another intriguing combination, and one that has the potential to act like an in situ vaccination that can lead to abscopal responses (ie, responses at distant sites), noted Harrington, something he has, thus far, only observed rarely with radiation.

“The idea behind combining checkpoint inhibition and radiation is that we could use the confluence of the two different mechanisms to make abscopal responses more predictable and more effective at a distant site, while engendering an immunologically relevant response that allows us to treat macroscopic metastatic disease while also getting rid of micrometastatic disease that could lead to metastatic failure,” he said.

Although immunotherapy combinations are showing promise in SCCHN and other cancers, the panelists warned that they should only be attempted as part of clinical trials. “There are still a lot of question marks about combinations, so they must be done as part of a clinical trial,” said Seiwert. Not only are toxicities and immunosuppressive effects best managed in clinical trials, but trials are essential in advancing these therapies and identifying the next breakthroughs in the field, he said.

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

Every 50 cigarettes you smoke gives you one extra DNA mutation per lung cell.

Source: The Verge
Author: James Vincent

A common tactic for people trying to give up smoking is to quantify exactly how much damage — financial or physical — each cigarette or pack of cigarette does. How much does smoking cost you per month, for example, or how much shorter is your life going to be for each drag you take? Well, a new study into the dangers of smoking now lets us measure this damage right down to the number of mutations in your DNA.

A research team led by scientists from Los Alamos National Laboratory compared tissue samples from 1,063 non-smokers and 2,490 smokers, examining each individual’s DNA to look for mutations. They found that for every 50 cigarettes smoked, there is one extra DNA mutation for each cell in the lungs. Over the course of a year, this means that someone who smokes a pack a day (20 cigarettes) has 150 extra mutations per cell in the lung, 97 per larynx cell, 23 per mouth cell, 18 per bladder cell, and six per liver cell.

These changes to the cells aren’t dangerous in themselves, but each one has the potential to turn into a cancerous growth. “Smoking is like playing Russian roulette: the more you play, the higher the chance the mutations will hit the right genes and you will develop cancer,” Ludmil Alexandrov, the co-lead author of the study, told the New Scientist. “However, there will always be people who smoke a lot but the mutations do not hit the right genes.”

The reason for all these extra mutations is found in tobacco smoke — a substance that contains some 7,000 different chemicals, over 70 of which are known to cause cancer. How exactly different types of cell mutations lead to cancer is less clear, and the team from Los Alamos are hoping next to drill down further into this line of research and find out the probabilities that any individual DNA mutation will turn into cancer.

The good news for smokers, though, is that it’s never too late to quit. Although smoking causes regular DNA mutations, as soon as people give up cigarettes, the mutations stop too. One UK study from 2004 found that those who quit smoking at age 30 nearly eliminate the risk of dying prematurely, while those who quit at 50 halve it. For people trying to give up, those are certainly some more comforting odds.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.

There are many factors contributing to the massive rise in cancer cases in the US, but according to a new study from the American Cancer Society, cigarette smoke is by far the leading cause. The study found that roughly 25% of all cancer deaths could be attributed to cigarette smoking.

Although cigarette smoking has waned somewhat in recent years, nearly 40 million adults in the U.S. currently smoke cigarettes. The CDC says cigarette smoking is the leading cause of preventable disease and death in the U.S., responsible for more than 480,000 deaths annually.

According to the study:

We estimate that at least 167133 cancer deaths in the United States in 2014 (28.6% of all cancer deaths; 95% CI, 28.2%-28.8%) were attributable to cigarette smoking. Among men, the proportion of cancer deaths attributable to smoking ranged from a low of 21.8% in Utah (95% CI, 19.9%-23.5%) to a high of 39.5% in Arkansas (95% CI, 36.9%-41.7%), but was at least 30% in every state except Utah. Among women, the proportion ranged from 11.1% in Utah (95% CI, 9.6%-12.3%) to 29.0% in Kentucky (95% CI, 27.2%-30.7%) and was at least 20% in all states except Utah, California, and Hawaii. Nine of the top 10 ranked states for men and 6 of the top 10 ranked states for women were located in the South. In men, smoking explained nearly 40% of cancer deaths in the top 5 ranked states (Arkansas, Louisiana, Tennessee, West Virginia, and Kentucky). In women, smoking explained more than 26% of all cancer deaths in the top 5 ranked states, which included 3 Southern states (Kentucky, Arkansas, and Tennessee), and 2 Western states (Alaska and Nevada).

Smoking is one of the leading causes of illness and death in the world. The use of tobacco has become more widespread than ever and the substance itself is far more dangerous than it has ever been before.

Today, cigarettes are mass produced and treated with thousands of additives and chemicals. Carcinogenic, poisonous chemicals and toxic metals can all be found in modern tobacco products. These chemicals are present for many reasons ranging from taste and preservation to being purposely addictive. There are over 4000 of these chemicals in cigarettes and all of them are not revealed to the public. They are protected under law as “trade secrets” — meaning they can add anything they want in there without our knowledge.

The financial advantage alone should be enough of an argument to quit smoking. In most states, cigarettes are now over 6 dollars a pack, more than half of which is taxes. So people are literally paying the government and rich multinational corporations an average of 10 dollars every day, for a product that destroys their bodies. It is true that there are addictive chemicals in cigarettes but their strength and power has been blown way out of proportion.

The psychological addiction is always much stronger than the physical addiction even with harsh narcotics like heroin and especially with nicotine. All you have to do is stop and get through a few days without it. Soon enough the smell and taste will no longer be desirable to you and you will be happy to have that extra 6 dollars a pack in your pocket. It will be easier to breathe, you won’t get sick as often and you will overall be in better spirits. Quitting cigarettes is one decision that you can make that will drastically improve your life in a number of ways and it will give the elite less control of your money and your health.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

There was another big win in the advancement of immunotherapy treatments for cancer this week.

The Food and Drug Administration approved an immunotherapy drug called Keytruda, which stimulates the body’s immune system, for the first-line treatment of patients with metastatic non-small-cell lung cancer.

In other words, the drug could be the very first treatment a patient receives for the disease, instead of chemotherapy. Keytruda is the only immunotherapy drug approved for first-line treatment for these patients.

So it seems, the future of cancer care may be in our own immune systems, but how exactly does it work, and what are its pros and cons?

“It’s certainly going to become an independent way of treating cancers,” said Dr. Philip Greenberg, head of immunology at the Fred Hutchinson Cancer Research Center in Seattle, during a Q&A session at the International Cancer Immunotherapy Conference in New York in September.

“We always talk about the three pillars of cancer therapy — radiation therapy, chemotherapy and surgery — and it’s become quite clear now that there’s going to be a fourth pillar, which is immunotherapy,” he said. “There are times where it will be used alone, and there will be times that it will be used in conjunction with the other therapies, but there’s very little to question that this is going to be a major part of the way cancers are treated from now on, going forward.”

Here’s a look at the past, present and future of cancer immunotherapy.

It began with Bessie

In the summer of 1890, 17-year-old Elizabeth Dashiell, affectionately called “Bessie,” caught her hand between two seats on a passenger train and later noticed a painful lump in the area that got caught, according to the Cancer Research Institute.

She met with a 28-year-old physician named Dr. William Coley in New York to address the injury. He performed a biopsy, expecting to find pus in the lump, probably from an infection. But what he found was more disturbing: a small gray mass on the bone. It was a malignant tumor from a type of cancer called sarcoma.

Dashiell had her arm amputated to treat the cancer, but the disease quickly spread to the rest of her body. She died in January 1891. A devastated Coley went on to devote his medical career to cancer research.

Coley is sometimes referred to as the “father of cancer immunotherapy,” according to the Memorial Sloan Kettering Cancer Center.

During his career, he noticed that infections in cancer patients were sometimes associated with the disease regressing. The surprising discovery prompted him to speculate that intentionally producing an infection in a patient could help treat cancer.

To test the idea, Coley created a mixture of bacteria and used that cocktail to create infections in cancer patients in 1893. The bacteria would sometimes spur a patient’s immune system to attack not only the infection but also anything else in the body that appeared “foreign,” including a tumor. In one case, when Coley injected streptococcal bacteria into a cancer patient to cause erysipelas, a bacterial infection in the skin, the patient’s tumor vanished — presumably because it was attacked by the immune system.

Coley’s idea was occasionally studied by various researchers in the 1900s but was not widely accepted as a cancer treatment approach until more recently.

“Immunotherapy has essentially undergone a sort of revolution in the last decade in the sense that something that was experimental — and there were still questions about what role it would have in the way cancer is treated — is completely turned around, and now it’s clear it’s effective,” Greenberg said.

German physician Dr. Paul Ehrlich, who won the Nobel Prize in physiology or medicine in 1908, proposed using the immune system to suppress tumor formation in the “immune surveillance” hypothesis — an idea that seems to follow Coley’s.

Yet it wasn’t until the early 2000s that the hypothesis became more widely accepted, according to the Cancer Research Institute. A landmark review published in the journal Nature Immunology in 2002 supported the validity of cancer immunosurveillance.

“Cancer immunotherapy really refers to treatments that use your own immune system to recognize, control and hopefully ultimately cure cancers,” said Jill O’Donnell-Tormey, CEO of the Cancer Research Institute, during the conference in New York last month.

“Many people for many years didn’t think the immune system was really going to have a role in any treatment for cancer,” she said, “but I think the entire medical community (and) oncologists now agree that immunotherapy’s here to stay.”

‘Turning oncology on its head’

One of the most famous cancer patients to have received a form of immunotherapy is former President Jimmy Carter, who had a deadly form of skin cancer called melanoma. Last year, he announced that he was cancer-free after undergoing a combination of surgery, radiation and immunotherapy.

Carter was taking Keytruda. It’s approved to treat melanoma, non-small-cell lung cancer, and head and neck cancer. However, it’s not the only approved immunotherapy option out there.

“The advances and the results we’ve seen with using the immune system to treat cancer in the last five years or so are turning the practice of oncology on its head,” said Dr. Crystal Mackall, a professor at the Stanford University School of Medicine and expert on cancer immunotherapy.

You don’t want to overstate it. As an immunotherapist, I see things from my vantage point, which is biased, but my clinical colleagues use words like ‘revolution,’ ” she said. “When I hear them say that, I think, ‘Wow, this really is a paradigm shifting for how we think about treating cancer.’ ”

Immunotherapy comes in many forms — treatment vaccines, antibody therapies and drugs — and can be received through an injection, a pill or capsule, a topical ointment or cream, or a catheter.

The FDA approved the first treatment vaccine for cancer, called sipuleucel-T or Provenge, in 2010. It stimulates an immune system response to prostate cancer cells and was found in clinical trials to increase the survival of men with a certain type of prostate cancer by about four months.

Another treatment vaccine, called T-VEC or Imlygic, was approved by the FDA in 2015 to treat some patients with metastatic melanoma.

Some antibody therapies have been approved, as well. Antibodies, a blood protein, play a key role in the immune system and can be produced in a lab to help the immune system attack cancer cells.

The FDA has approved several antibody-drug conjugates, including Kadcyla for the treatment of some breast cancers, Adcetris for Hodgkin lymphoma and a type of non-Hodgkin T-cell lymphoma, and Zevalin for a type of non-Hodgkin B-cell lymphoma.

The FDA also has approved some immunotherapy drugs known as immune checkpoint inhibitors. They block some of the harm that cancer cells can cause to weaken the immune system.

Keytruda, which Carter took, is a checkpoint inhibitor drug. Other such drugs include Opdivo to treat Hodgkin lymphoma, advanced melanoma, a form of kidney cancer and advanced lung cancer. Tecentriq is used to treat bladder cancer, and Yervoy is used for late-stage melanoma.

Additionally, there are many immunotherapy treatments in clinical trials, such as CAR T-cell therapy. The cutting-edge therapy involves removing T-cells from a patient’s immune system, engineering those cells in a lab to target specific cancer cells and then infusing the engineered cells back into the patient. The treatment is being tested to treat leukemia and lymphoma.

“The real excitement now in cellular therapy, in T-cell therapies, is it reflects the developments in an area that we call synthetic biology, which is that you can add genes to cells and you can change what they do, how they behave, how they function, what they recognize,” Greenberg said.

The high price of new immunotherapy drugs has also garnered attention in the field, according to the Fred Hutchinson Cancer Research Center. For instance, some estimates suggest that checkpoint inhibitor treatments could cost as much as $1 million per patient.

As approvals continue, many scientists caution that doctors and patients alike should prepare for potential severe side effects and downsides.

Boosting the immune system with such therapies may cause skin reactions, flu-like symptoms, heart palpitations, diarrhea and a risk of infection. New cancer immunotherapy drugs have even been linked to arthritis in some patients.

A clinical trial conducted by Juno Therapeutics to test the effectiveness of an experimental immunotherapy treatment for lymphoblastic leukemia was halted after three patients died. They suffered cerebral edema or brain swelling.

Greenberg is a scientific co-founder of Juno Therapeutics.

However, “one of the best attributes of immunotherapy and the future of medicine is that it’s very precise in the way that it kills tissue and spares normal tissue, so in some way, immunotherapy is less toxic (than other therapies). There are patients who are treated with checkpoint inhibitors who have essentially no side effects,” Mackall said. “That would never happen with chemotherapy. They would always have side effects.

“Still, you know, the fact remains that probably nothing is perfect, and there are likely to be some side effects, but as far as we know now, they are less likely to be as severe or prevalent.”

As immunotherapy continues to develop as an option for cancer treatment, experts plan to be realistic about forthcoming challenges.

The challenges of immunotherapy

Experts say they hope to better understand why some patients may have different responses to immunotherapy treatments than others — and why some treatments may result in remissions instead of relapses, or vice versa.

“There’s this whole problem of, you give people an immunotherapy, it looks like it’s working, and then it stops working. We get recurrences or progression after some period, and the question is, why did that happen? How can you change it?” Greenberg said.

“This is where the science has come to play an important part: Is it because the immune response was working and somehow the tumor turned it off? And if that’s the case, then we have to look at ways in which we can reactivate the immune system,” he said. “Or is it not that, is it just that the immune system did what it’s supposed to do, but now a variant grew out, now a tumor grew out that’s no longer recognized by the immune response you are enforcing? If that’s the case, then we need ways to build subsequent immune responses to tackle that.”

Therefore, researchers have to better understand the behavior of not only the immune system but also cancerous tumors — and it’s no simple task.

“If there’s a perception that it’s easy, that’s a mistake. I think our lab has spent decades trying to figure out how to manipulate the immune response,” Greenberg said.

“Some patients are anticipating things to change overnight and be immediately available as a therapy. It takes quite a while,” he said, “but I’m quite certain immunotherapy is going to be enormously useful. It’s just, right now, we are limited in what can be done.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy

When the Republican-controlled Congress approved a landmark program in 2003 to help seniors buy prescription drugs, it slapped on an unusual restriction: The federal government was barred from negotiating cheaper prices for those medicines. Instead, the job of holding down costs was outsourced to the insurance companies delivering the subsidized new coverage, known as Medicare Part D.

The ban on government price bargaining, justified by supporters on free-market grounds, has been derided by critics as a giant gift to the drug industry. Democratic lawmakers began introducing bills to free the government to use its vast purchasing power to negotiate better deals even before former President George W. Bush signed the Part D law, known as the Medicare Modernization Act.

All those measures over the last 13 years have failed, almost always without ever even getting a hearing, much less being brought up for a vote. That’s happened even though surveys have shown broad public support for the idea. For example, a Kaiser Family Foundation poll found last year that 93 percent of Democrats and 74 percent of Republicans favor letting the government negotiate Part D prescription drug prices.

“I mean, how in the world can one explain that the government actually passed a law saying that you can’t negotiate prices?”

It seems an anomaly in a democracy that an idea that is immensely popular—and calculated to save money for seniors, people with disabilities, and taxpayers—gets no traction. But critics say it’s no mystery, given the enormous financial influence of the drug industry, which rivals the insurance industry as the top-spending lobbying machine in Washington. It has funneled $1.96 billion into lobbying in the nation’s capital since the beginning of 2003 and, in just 2015 and the first half of 2016, has spent the equivalent of $468,108 per member of Congress. The industry also is a major contributor to House and Senate campaigns.

“It’s Exhibit A in how crony capitalism works,” said Rep. Peter Welch (D-Vt.), who has sponsored or co-sponsored at least six bills since 2007 to allow Part D drug price negotiations. “I mean,” he added, “how in the world can one explain that the government actually passed a law saying that you can’t negotiate prices? Well, campaign contributions and lobbying obviously had a big part in making that upside-down outcome occur.”

Wendell Potter, co-author of a book about the influence of money in politics, Nation on the Take, likened the drug industry’s defiance of public opinion to the gun lobby’s success in fending off tougher federal firearms controls and the big banks’ ability to escape stronger regulation despite their role in the Great Recession.

“They are able to pretty much call the shots,” Potter said, referring to the drug industry along with its allies in the insurance industry. “It doesn’t matter what the public will is or what public opinion polls are showing. As long as we have a system that enables industries, big corporations, to spend pretty much whatever it takes to influence the elections and public policy, we’re going to wind up with this situation.”

While Part D is only one of the issues the drug industry pushes in Washington, it is a blockbuster program. According to a report from the trustees of the Medicare system, this year Part D is expected to spend $103 billion to serve an estimated 43 million Americans.

A paper released in August by Harvard Medical School researchers cited the size of the program and its lack of government negotiating clout as among the reasons why Americans pay the highest prices in the world for prescription drugs. A co-author of that paper, Ameet Sarpatwari, estimates that Part D accounts for nearly 30 percent of the nation’s spending on prescription drugs.

What’s more, Part D often pays far more for drugs than do Medicaid or the Veterans Health Administration—which, unlike Part D, mandate government measures to hold down prices. One report found that Part D pays 80 percent more for medicines than the VHA and 73 percent more than Medicaid. While researchers aren’t unanimous in their views, an array of experts have concluded that federal negotiating power—if backed up by other cost controls—would bring Part D drug costs more in line.

The drug industry and its allies acknowledge that, at least in the short term, federal intervention in the marketplace could bring lower drug prices. Yet the industry says such a step would also kill incentives to develop new medicines.

In addition, industry officials and many analysts say substantial cost reductions will come only if the Part D program refuses to pay for drugs that it considers overpriced, possibly reducing seniors’ access to some medicines. They point to the way the VHA strengthens its negotiating leverage by rejecting some expensive medicines. Instead, the veterans’ health care system limits its purchases to a list of approved drugs known as a formulary.

“If you want to have lower prices, you’re going to have fewer medicines,” said Kirsten Axelsen, a vice president at Pfizer, a pharmaceutical giant that leads all drug companies in spending on lobbying and political campaigns at the federal level.

It took intense maneuvering by the Bush White House and GOP leaders to get Part D through Congress in November 2003, when the House and the Senate were under Republican control. The measure came up for a vote in the House at 3 a.m. on the Saturday before Thanksgiving, as lawmakers were trying to finish business before the holiday. But when the bill appeared headed to a narrow defeat after the normal 15 minutes allowed for voting, Republican leaders kept the vote open for an extraordinary stretch of nearly three hours, described in a 2004 scholarly paper as by far the longest known roll-call vote in the history of the House.

With the help of pre-dawn phone calls from Bush and a custom-defying visit to the House floor by Tommy Thompson, then secretary of health and human services, enough members were coaxed to switch their votes to pass the bill, 220-215, shortly before 6 a.m.

Part D was conceived at a time when rapidly rising US drug costs were alarming seniors, prompting some to head to Canada and Mexico to buy medicines at dramatically lower prices. With the 2004 presidential election campaign coming up, Republican leaders saw “an opportunity to steal a long-standing issue from the Democrats,” said Thomas R. Oliver, a health policy expert at the University of Wisconsin-Madison and the lead author of the 2004 paper about the adoption of Part D.

Last year the drug industry retained 894 lobbyists to influence the 535 members of Congress, staffers, and regulators.

A key aim of Part D proponents, Oliver said, was to cover seniors “in a Republican, pro-market kind of way.” That meant including “as much private sector involvement as possible,” which led to insurance companies managing the program. At the same time, it excluded federal price controls, which were anathema to the drug industry.

Today, the program remains subject to the pervasive influence of the drug industry. An analysis by FairWarning, based on spending data provided by the Center for Responsive Politics, a nonprofit and nonpartisan research group, has found:

— There are far more lobbyists in Washington working for drug manufacturers and wholesalers than there are members of Congress. Last year the industry retained 894 lobbyists to influence the 535 members of Congress, along with staffers and regulators. From 2007 through 2009, there were more than two drug industry lobbyists for every member of Congress.

— For each of the last 13 years, more than 60 percent of the industry’s drug lobbyists have been “revolvers”—that is, lobbyists who previously served in Congress or who worked as congressional aides or in other government jobs. That raises suspicions that lawmakers and regulators will go easy on the industry to avoid jeopardizing their chances of landing lucrative lobbying work after they leave office.

Probably the most notorious example was the Louisiana Republican Billy Tauzin. He helped shape the Part D legislation while serving as chairman of the House Energy and Commerce Committee. In January 2005, just days after he retired from the House, he became the drug industry’s top lobbyist as president of a powerful trade group, the Pharmaceutical Research and Manufacturers of America, or PhRMA. He remained in that job—which reportedly paid him $2 million a year—until 2010.

“It was pretty blatant but an accurate reflection of the way pharma plays the game, through campaign contributions and, in Billy’s case, way more than that,” said US Rep. Jan Schakowsky, an Illinois Democrat who has been a leading proponent of government price negotiations.

— Since January 2003, drug manufacturers and wholesalers have given $147.5 million in federal political contributions to presidential and congressional candidates, party committees, leadership PACs and other political advocacy groups. Of the total, 62 percent has gone to Republican or conservative causes.

Over the period, four Republican lawmakers from the 2015-16 Congress received more than $1 million in contributions from drug companies. (One of them, former House Speaker John Boehner, R-Ohio, resigned last October.) In all, 518 members of the current Congress—every member of the Senate and more than 95 percent of the House—have received drug industry money since 2003.

Pfizer said that since the beginning of 2003 through the middle of this year it has spent, at the federal level, $145.9 million on lobbying as well as $12.2 million on political contributions through its PACs. In a written statement, the company said, “Our political contributions are led by two guiding principles—preserve and further the incentives for innovation, and protect and expand access for the patients we serve.”

— The big money goes to top congressional leaders as well as chairs and other members of key committees and subcommittees.

The House Energy and Commerce Health Subcommittee, repeatedly a graveyard for Part D price negotiation bills, underscores the pattern. The 16 Republican members have received an average of $340,219 since the beginning of 2003.

The drug industry “knows that you really only need, in many cases, just a small number of influential members to do their bidding. That’s why you see contributions flowing to committee chairs, regardless of who is in power. They flow to Democrats as well as Republicans,” Potter said.

Proponents of negotiations say some economic and political currents may turn the tide in their favor. The main factor: After years of relatively modest price rises for prescription drugs, cost increases have begun to escalate. That’s partly because of expensive new treatments for illnesses such as hepatitis C.

According to Medicare officials, Part D payments are expected to rise 6 percent annually over the coming decade per enrollee, up from only 2.5 percent annually over the last nine years. Already, cost increases are “putting wicked pressure on our hospitals, on our seniors, and on our state governments,” Welch said.

At the same time, both major presidential candidates, Hillary Clinton and Donald Trump, have called for Medicare drug price negotiation. So have doctor groups such as the American College of Physicians and an alliance of more than 100 oncologists, many nationally known, who last year garnered headlines with their plea for Medicare negotiations and other measures to fight skyrocketing costs for cancer drugs.

PhRMA, the trade group, wouldn’t comment for this story on lobbying or campaign spending. In a written statement, however, PhRMA spokeswoman Allyson Funk said, “There is significant price negotiation that already occurs within the Medicare prescription drug program.” Pointing to the private companies that run the program, Funk added, “Large, powerful purchasers negotiate discounts and rebates directly with manufacturers, saving money for both beneficiaries and taxpayers.”

Funk also pointed to skeptical assessments by the Congressional Budget Office about the potential additional savings from federal negotiations. Repeatedly—including in letters in 2004 and 2007—the CBO has said government officials likely could extract only modest savings, at best. The office’s reasoning is that costs already would be held down by bargaining pressure from insurance firms and by drug manufacturers’ fear of bad publicity if they are viewed as jacking up prices too high.

But many analysts, particularly amid recent controversies over skyrocketing costs for essential drugs and EpiPen injection devices, scoff at those CBO conclusions. They fault the CBO for not taking into account other price controls, such as those used by Medicaid and the VHA, that likely would be coupled with price negotiation.

“You would want Medicare to have the option to say, ‘Okay, this is our price, and you’re going to take it. And if you don’t take it, we’re not buying it.'”

What CBO officials “seem to be assuming is that Congress would change the law in a really foolish way,” said Dean Baker, a liberal think tank economist who has studied the Part D program. “It seems to me that if you got Congress to change the law, you would want Medicare to have the option to say, ‘Okay, this is our price, and you’re going to take it. And if you don’t take it, we’re not buying it.”

In fact, related bills proposed during the current Congress by two Illinois Democrats—Schakowsky and Richard J. Durbin, the Senate minority whip—go beyond requiring drug price negotiations. They both provide for federal officials to adopt “strategies similar to those used by other Federal purchasers of prescription drugs, and other strategies…to reduce the purchase cost of covered part D drugs.”

The potential to reduce prices is underscored by a 2015 paper by Carleton University of Ottawa, Canada, and the US advocacy group Public Citizen. It found that Medicare Part D on average pays 73 percent more than Medicaid and 80 percent more than the VHA for the same brand-name drugs. The VHA’s success in holding down costs helped inspire a measure on California’s November ballot, Proposition 61, that would restrict most state-run health programs from paying any more for prescription drugs than the veterans agency does.

Two studies by the inspector general of health and human services that compared drug expenditures under the Part D and Medicaid programs also concluded that Part D pays far more for the same medicines. The more recent inspector general study, released in April 2015, examined spending and rebates on 200 brand-name drugs. It found that, after taking rebates into account, Medicaid, which provides health care for low-income families with children, paid less than half of what Part D did for 110 of the drugs. Part D, on the other hand, paid less than Medicaid for only 5 of 200 drugs.

Those findings provide evidence that “the current reliance on private insurers that negotiate drug prices isn’t working that well,” said Edwin Park, vice president for health policy at the Center on Budget and Policy Priorities, a Washington think tank.

Five Democrats who are leading opponents of the status quo—US Representatives Welch, Schakowsky, and Elijah E. Cummings of Maryland, along with Sens. Durbin and Amy Klobuchar of Minnesota—each have introduced price negotiation bills (HR 3061, HR 3261, HR 3513, S 31 and S 1884) during the current, 114th Congress. All the measures have stalled in committee.

Schakowsky, a House Democratic chief deputy whip, said under Republican control in her chamber, “I think it is virtually impossible for this to ever go to hearings and markups.”

Take, for example, the bill that Welch introduced in the House on July 14, 2015. Within a week, it was referred to two health subcommittees, where it has sat ever since.

The closest Welch ever came to success was in 2007. He was among 198 co-sponsors—all but one, Democrats—of a bill introduced by then-US Rep. John D. Dingell of Michigan. It was approved by the House but then blocked by Republicans from being taken up in the Senate.

“There’s a lot of industry opposition…It doesn’t mean, however, that industry is all-powerful.”

Lawmakers on committees where Part D bills ordinarily go—the Finance Committee in the Senate, and the Energy and Commerce Committee as well as the Ways and Means Committee in the House—tend to be well funded by the drug industry.

For instance, Sen. Richard Burr (R-N.C.), who sits on the Finance Committee, has received more money from the industry since 2003 than anyone else currently in Congress, $1.3 million. Close behind is Senate Finance Chairman Orrin Hatch, (R-Utah), who has gotten $1.18 million. (The other members of the million-dollar club are Rep. Fred Upton (R-Mich.), House Energy and Commerce chairman, at $1 million, and former House Speaker Boehner, at $1.21 million.)

Burr also is the Senate leader so far in the 2015-16 political cycle, collecting $229,710 from the drug industry. In the House in the current cycle, John Shimkus (R-Ill.), a member of the Energy and Commerce health subcommittee, has snagged $189,000, trailing only Republican Majority Leader Kevin McCarthy ($292,550) and House Speaker Paul Ryan ($273,195). A Burr spokeswoman declined to comment. Hatch and Shimkus did not respond to repeated requests for comment.

Amid the EpiPen controversy and growing concerns about prescription drug prices, Park sees signs that more lawmakers are willing to buck industry opposition to government price negotiation. “There’s a lot of industry opposition. This would affect their bottom line,” Park said. “It doesn’t mean, however, that industry is all-powerful.”

But Baker, co-director of the Center for Economic and Policy Research in Washington, was skeptical about the prospects for reform. “I think it’s pretty clear what you’re seeing is, there’s an industry group that stands to lose a lot of money, and they’re basically using all of the political power they can to make sure that it doesn’t happen.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

U.S. regulators approved a vaccine to protect against the human papilloma virus (HPV) in 2006, but cancer experts say misconceptions and stigma continue to hamper acceptance by both doctors and parents.

Eighty percent of Americans are exposed to the human papilloma virus in their lifetimes. Some strains of HPV can cause genital warts, but most people experience no symptoms and clear the virus from their systems within a year or two. But for an unlucky minority, the virus causes damage that, years later, leads to cervical cancer, throat cancer, and other types.

Researchers at MD Anderson are frustrated that ten years after the first vaccine arrived on the market, only 42 percent of U.S. girls, and 28 percent of boys, are getting the three-shot series.

The series can be given to girls and boys between the ages of 9 and 26, but the immune response is strongest at younger ages, before sexual activity begins.

n 2007, then-Texas governor Rick Perry proposed making the HPV vaccine mandatory for all preteen girls. At the time, the vaccine was only approved and marketed for girls.

“A lot of people felt that was the right idea, but the wrong way to go about it. Nobody really likes being told what to do, especially in Texas,” Ramondetta said. “I think there was a lot of backlash.”

Eventually, the legislature rejected Perry’s plan, even though it included an opt-out provision. Ramondetta said too many politicians focused on the fact that HPV is sexually transmitted. That had the unfortunate effect of skewing the conversation away from health care and into debates about morality and sexuality. She said the best and most accurate way to discuss the vaccine is to describe it as something that can prevent illness and death.

“I try to remove the whole concept of sexuality,” Ramondetta said. “When you’re talking about an infection that infects 80 percent of people, you’re really talking about something that is part of the human condition. Kind of like, it’s important to wash your hands because staph and strep are on all of us.”

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

Kara Million of League City finds those numbers upsetting. Million survived two rounds of treatment for cervical cancer.

“Even if you had a chance that your kid could have any kind of cancer, and you could have given them two shots or three shots for it? To me, it’s a no-brainer,” Million said.

Million always got regular Pap tests. But she missed one appointment during a busy time following the birth of her second child. When she went back, it had been only 15 months since her last Pap test. But the doctor found cervical cancer, and it had already progressed to stage 3.

“That was a huge surprise,” Million recalled.

Million had chemotherapy and radiation at MD Anderson. But a year later the cancer returned.

The next step was surgery, a radical procedure called a total pelvic exenteration.

Million and her husband looked it up online.

“When I was reading it, I was just, like, ‘this is so barbaric, there is no way they are still doing this in this day and age,’” Million said. “‘For certain, in 2010 we have better surgeries to do than this.’”

But there weren’t better surgeries. This was her only option.

“I had a total hysterectomy; they pulled all the reproductive system out,” she explained. “They take your bladder out, they take part of your rectum, they take part of your colon, they take your vagina, all of that in your pelvic area comes out.”

The surgery took 13 hours, and left her with a permanent colostomy bag and urostomy bag.

“At that point, with two kids at that age – I think they were one-and-a-half and three – there’s no option. I’m a mom, so I’m going to do whatever it takes so they can have their mom.”

Most women survive cervical cancer if it’s caught early enough. But Million’s cancer was diagnosed at a later stage, where only a third of women make it past five years. She has already made it past that five-year anniversary, and she’s not wasting any time.

She now volunteers as a peer counselor at MD Anderson to other cervical cancer patients, and she urges parents to vaccinate their kids.

“If most of cervical cancer is caused by HPV, and now we have something that can help prevent what I went through, and what my friends went through, and the friends that I lost?” Million says, “I don’t understand why people don’t line up at the door to get their kids vaccinated for it.”

But Dr. Ramondetta said parents can’t consent to the vaccination if pediatricians or family doctors don’t offer it. And they’re not offering it nearly enough, she said.

Some doctors don’t know how to broach the topic, fearing it will lead to a difficult conversation about sexual behavior. Some mistakenly think boys don’t need it, although they do – not only to protect their partners from HPV, but to protect themselves against oropharyngeal and anal cancers, which are also caused by HPV. Ramondetta added that some doctors incorrectly assume that giving the vaccine will promote promiscuity.

Ramondetta says extensive research actually shows it doesn’t.

“There should be this understanding of an ethical responsibility. That this is part of cancer screening and prevention, just like recommending mammograms and colonoscopies.”

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

The FDA approval of pembrolizumab (Keytruda) as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in August 2016 was extremely significant for this patient population, which previously had limited options following progression on a platinum-based chemotherapy.

The approval was based on the phase Ib KEYNOTE-012 study, which demonstrated that pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.

Several other studies are further evaluating the immunotherapy agent in HNSCC.Preliminary results of the phase II KEYNOTE-055 study—which included 92 evaluable patients who received pembrolizumab after failing platinum and cetuximab therapies—were presented at the 2016 ASCO Annual Meeting.

In an interview with Targeted Oncology, lead study author Joshua M. Bauml, MD, an assistant professor of Medicine, Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center, discusses the impact of pembrolizumab’s success in HNSCC, the results of the KEYNOTE-055 study, and what he sees on the horizon for the PD-1 inhibitor in this field.

TARGETED ONCOLOGY:What role do you envision pembrolizumab having in this patient population?

Baumi: It is going to play a critical role in head and neck cancer. The other agents that are available have limited efficacy, and are associated with significant toxicities. This is a clear improvement for our patient population with limited options.

TARGETED ONCOLOGY: What were the key takeaways from KEYNOTE-055? Baumi: Patients with recurrent/metastatic head and neck cancer that is refractory to both platinum-based therapy and cetuximab (Erbitux) really have very few options. The historical reference population we usually use is patients treated with methotrexate, which has a response rate of 5% and an overall survival (OS) of only about 6 months. There is a really great need for this. For pembrolizumab, which is an anti–PD-L1 agent, there is biologic rationale to think that it would be active in this patient population. PD-L1 and PD-L2 are unregulated in head and neck cancer.

What KEYNOTE-055 did is really try and create a homogenous patient population. Rather than a large phase I study, here are patients all who have failed both platinum-based therapy and cetuximab. We have really identified the sickest patient population.

What we are able to show in this study was that the drug was well tolerated and it has a response rate of 17% to 18%, which compares favorably for the 5% seen with the prior data with methotrexate. The OS rate was 8 months, which again compares very favorably to the 6 months seen with methotrexate. This was true, even though 85% of patients had received at least 2 prior treatments for head and neck cancer.

TARGETED ONCOLOGY: What did this study tell us about the safety of pembrolizumab in head and neck cancer?

Baumi: The rate of grade 3 through 5 treatment-related adverse events was 12% in our study. Nearly all of the side effects are what you would expect with pembrolizumab; those have been reported in multiple other studies. There was 1 treatment-related death due to pneumonitis, which is a rare side effect of this class of drugs.

Outside of that, it was a really well-tolerated agent. The fact that if you compared grade 3 through 5 toxicities of 12% with cytotoxic chemotherapy, this is a very well-tolerated agent.

TARGETED ONCOLOGY: How common is it for patients to fail both platinum-based therapy and cetuximab?

Baumi: Any patient who has recurrent or metastatic head and neck cancer is going to go through these agents if they survive long enough to get them. Basically, we know that these are the limited tools in our toolbox. We have platinum, we have cetuximab, and then we are really out of options. Many patients have received cetuximab in the locally advanced setting and so we have already lost one of our active treatments. This affects a lot of people.

TARGETED ONCOLOGY: What is next for pembrolizumab in head and neck cancer?

Baumi: There are currently phase III studies evaluating pembrolizumab in head and neck cancer both in combination with and versus traditional cytotoxic chemotherapy to see if we can move up the treatment earlier for patients. The key difference between pembrolizumab and cytotoxics is beyond the improved safety profile. However, we have durable responses; 75% of those patients who responded are still responding to this day. That is really not something that we see.

TARGETED ONCOLOGY: What are the biggest questions that remain regarding the treatment of patients with metastatic head and neck cancer?

Baumi: One of the key questions that relates to immunotherapy—and this covers all tumors—is trying to identify who the 20% of patients are that will respond. Eighty percent of our patients are not responding to our therapies.

Identifying a biomarker to enrich this patient population is very critical. Right now, I would not select patients for pembrolizumab by virtue of PD-L1 status because there were responses in the PD-L1–negative cohorts.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.